Breaking News
March 21, 2018 - Researchers develop statistics-based computational scheme to zoom in on brain function
March 21, 2018 - Verge joins Genomics England’s Discovery Forum industry partnership
March 21, 2018 - Trovagene Announces First Patient Successfully Completes Cycle 1 of Treatment with PCM-075 in Combination with Low Dose Cytarabine (LDAC) in AML Trial
March 21, 2018 - Congenital Cardiac Cath Tx Often Strays from Guidelines
March 21, 2018 - Marked increase in cardiovascular risk factors in women after preeclampsia
March 21, 2018 - New app may help predict, track manic and depressive episodes in bipolar patients
March 21, 2018 - Discovery of genes could lead to development of novel therapies for EBV-related cancers
March 21, 2018 - High-fat, high-cholesterol diet depletes ranks of artery-protecting immune cells
March 21, 2018 - Research misconduct allegations shadow likely CDC appointee
March 21, 2018 - Most Breast Ca Patients Fail to Get Genetic Counseling
March 21, 2018 - Lopsided ear function can lead to lopsided brain development
March 21, 2018 - Acupuncture helps manage menopausal symptoms, review finds
March 21, 2018 - Motor skill training may contribute to reading skills in obese children
March 21, 2018 - Poor dental health may be related to increased diabetes risk
March 21, 2018 - Chronic opioid users at increased risk of complications after spinal fusion surgery
March 21, 2018 - Scientists develop brain “stethoscope” that can detect silent seizures
March 21, 2018 - New method predicts effects of global warming on disease
March 21, 2018 - Insurance Company Hurdles Burden Doctors, May Harm Patients
March 21, 2018 - Renal Transplant from HCV-Positive Donors Feasible
March 21, 2018 - Myelodysplastic syndrome: MedlinePlus Medical Encyclopedia
March 21, 2018 - Research reveals brain mechanism involved in language learning
March 21, 2018 - Many parents still hesitate to try early peanut introduction, survey finds
March 21, 2018 - Audiologist urges tinnitus sufferers facing ‘revolving door healthcare’ to seek support
March 21, 2018 - Study reveals impact of prostate cancer on wives and partners of sufferers
March 21, 2018 - ‘Almost a Miracle Drug’: What We Heard This Week
March 21, 2018 - Study shows NIH spent >$100 billion on basic science for new medicines
March 21, 2018 - Columbia researchers identify nerve cells that drive fruit fly’s escape behavior
March 21, 2018 - Sartorius Stedim Biotech selected by ABL Europe to supply single-use process technologies
March 21, 2018 - Increase in coffee consumption may help battle against colon cancer
March 21, 2018 - Hydrogel may accelerate healing of diabetic ulcers
March 21, 2018 - Dermira’s Two Phase 3 Trials Evaluating Olumacostat Glasaretil in Patients with Acne Vulgaris Did Not Meet Co-Primary Endpoints
March 21, 2018 - DePuy Synthes introduces ACTIS Total Hip System for improving initial implant stability
March 21, 2018 - ‘Oh, It Was Nothing’
March 21, 2018 - Herbal drug kratom linked to salmonella illnesses, CDC says
March 21, 2018 - New optical point-of-care device could enhance screening for thyroid nodules
March 21, 2018 - FDA Expands Approval of Adcetris (brentuximab vedotin) for First-Line Treatment of Stage III or IV Classical Hodgkin Lymphoma in Combination with Chemotherapy
March 21, 2018 - Eosinophilic Esophagitis: Late Manifestation of Allergic March
March 21, 2018 - Signaling pathway involving the Golgi apparatus identified in cells with Huntington’s disease
March 21, 2018 - Quintupling inhaled steroid doses may not benefit children with asthma
March 21, 2018 - Study shows clear connection between cardiovascular fitness in middle age and dementia risk
March 21, 2018 - Premature babies have higher risks of health complications in Bangladesh
March 21, 2018 - Child’s temperament and parenting influence weight gain in babies
March 21, 2018 - Researchers find the heart to be capable of arrhythmia termination after local gene therapy
March 21, 2018 - Inhealthcare to provide digital infrastructure for NHS to help protect people from falls
March 21, 2018 - Flu Season Finally Slowing Down
March 21, 2018 - Mixed Results for Shorter DAPT in ACS Patients
March 21, 2018 - Scientists discover fish scale-derived collagen effective for healing wounds
March 21, 2018 - Genomics England announces new partnership to improve efficiency of next-generation sequencing analysis
March 21, 2018 - Adjuvant AC chemotherapy found to be effective in treating HRD-positive breast cancer patients
March 21, 2018 - Researchers identify new treatment targets for lung diseases using big data
March 21, 2018 - Kids see more women in science than five decades ago
March 21, 2018 - Research shows link between chronic fatigue syndrome and lower thyroid hormone levels
March 21, 2018 - Alzheimer’s disease on the rise
March 21, 2018 - Two Agents Equal as Pretreatment for Adrenal Tumor Surgery
March 21, 2018 - ‘Icebreaker’ protein opens genome for T cell development, researchers find
March 21, 2018 - Women in medicine shout #Metoo about sexual harassment at work
March 21, 2018 - Mother’s pre-pregnancy waist size may be linked to child’s autism risk
March 21, 2018 - Second hand marijuana smoke can cause serious damage
March 21, 2018 - International study shows benefits of using MRI at the start of prostate cancer diagnosis
March 20, 2018 - Santhera Reports Outcome of Exploratory Trial with Idebenone in PPMS Conducted at the NIH
March 20, 2018 - ECG Patch Ups At-Home Afib Diagnosis in mSToPS Trial
March 20, 2018 - ROS-scavenging nanozymes for anti-inflammation therapeutics
March 20, 2018 - Genomics England announces appointment of global genomics pioneer as first CEO
March 20, 2018 - Test flight at German Aerospace Center in Cologne demonstrates functionality of deficopter
March 20, 2018 - Music therapy helps treat combat-related psychological injuries in military personnel
March 20, 2018 - Innovative psychotherapeutic treatment protocol for obsessive-compulsive disorders
March 20, 2018 - Weight loss after lap-band surgery alleviates arthritic knee pain
March 20, 2018 - New diabetes drug may help obese people shed body weight
March 20, 2018 - Novel Peanut OIT a Winner in Phase III Trial
March 20, 2018 - Can gene therapy be harnessed to fight the AIDS virus?
March 20, 2018 - Education and academic achievement can lessen effects of child abuse, neglect
March 20, 2018 - Researchers develop new algorithm to make CPR more effective
March 20, 2018 - Diabetes medication reduces chance of late miscarriage, premature birth among women with PCOS
March 20, 2018 - SSRIs may be more effective option for treating anxious youth, UC research shows
March 20, 2018 - Antibiotics could benefit women suffering from chronic bladder pain
March 20, 2018 - Health Highlights: March 16, 2018
March 20, 2018 - Interventional Radiology Has a Problem of ‘Unseen’ Value
March 20, 2018 - Antibodies show effectiveness for HIV prevention and promise for treatment and cure
March 20, 2018 - New 3-D-printed technology will improve radiology training
March 20, 2018 - New study identifies key role for particular gene in 16p11.2 deletion syndrome
UCLA researchers reveal reversibility of Friedreich’s ataxia in mouse models

UCLA researchers reveal reversibility of Friedreich’s ataxia in mouse models

image_pdfDownload PDFimage_print

In children and adults with Friedreich’s ataxia, an inherited disease that causes damage to the nervous system, a loss of coordination typically progresses to muscle weakness and can involve vision, diabetes, and other problems over the course of several years. Until now, mimicking those symptoms and progression in mice for research studies has been difficult.

UCLA researchers, after developing a mouse model of Friedreich’s ataxia that shows symptoms similar to patients, have found that many early symptoms of the disease are completely reversible when the genetic defect linked to the ataxia is reversed. The new findings, which still need to be replicated in humans, appear in the journal eLife.

“Remarkably, most of the dysfunction we were seeing in the mice was reversible even after the mice showed substantial neurologic dysfunction,” said Dr. Daniel Geschwind, the Gordon and Virginia MacDonald Distinguished Chair in Human Genetics, a UCLA professor of Neurology and Psychiatry, and senior author of the new work. “We were very surprised by the extent to which the mice improved since we had assumed that this degree of behavioral dysfunction would be due to cell loss”

Friedreich’s ataxia can begin causing symptoms in childhood or early adulthood. It causes a loss of coordination, or “ataxia,” that makes patients stumble and stagger, among other early symptoms. The disease is known to be caused by a genetic mutation in the gene FXN. The mutation leads to reduced levels of the protein encoded by FXN, called frataxin. While doctors can manage some specific symptoms, there are no current treatments.

“The lack of treatments for Friedreich’s Ataxia has been frustrating for many and has been, in part, due to the lack of good animal models of the disease,” said Geschwind. “There was really a need for a mouse model to help researchers determine the consequences of whole body reduction of frataxin.”

In the new work, Geschwind and colleagues developed a mouse in which the FXN gene can be blocked by a strand of RNA that’s controlled by an antibiotic. Higher levels of the antibiotic lead to more blockage of the gene, and therefore lower levels of frataxin protein. This system allowed the researchers to have tight control over frataxin levels throughout a mouse’s life, letting the mice develop normally for three months before administering antibiotic to turn down frataxin levels.

After 12 weeks with low frataxin levels, the study found, mice have symptoms similar to those seen in humans with the disease, including weight loss, ataxia, impaired walking, hunched backs, and reduced muscular strength. When the researchers stopped giving antibiotics to the diseased mice, letting frataxin levels return to normal, most of the symptoms disappeared.

The study findings suggest that “quite a bit of dysfunction that’s being seen in patients, in the first few years of disease, represents reversible neuronal dysfunction rather than cell death and loss of neurons,” said Geschwind.

The researchers also used the mouse model to study which other genes and proteins are immediately affected by reductions in frataxin, helping point the way toward new drug targets. They hope to continue this line of work, studying the biochemical changes that occur in conjunction with Friedrich’s ataxia. They’re also making this model available for academic and commercial laboratories that are already pursuing drugs that aim to increase frataxin levels in human patients. In these cases, the new mouse model can be used to test the effectiveness of the drugs.

“Going forward, this model provides an important new potential avenue for therapeutic development,” said Geschwind.​

Tagged with:

About author

Related Articles